Phosphorus oxychloride → Benzhydryl 7-(2-benzyloxycarbonylmethoxyimino-4-bromo-3-oxobutyramido)-3-vinyl-3-cephem-4-carboxylate

HRID 1656181Notes

Reaction equation

HRID 1656181 reaction equation
P(Cl)(Cl)(Cl)=O.[CH2:6]([O:13][C:14]([CH2:16][O:17][N:18]=[C:19]([C:23](=[O:26])[CH2:24][Br:25])[C:20]([OH:22])=O)=[O:15])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Cl.[NH2:28][CH:29]1[C:54](=[O:55])[N:31]2[C:32]([C:38]([O:40][CH:41]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)=[O:39])=[C:33]([CH:36]=[CH2:37])[CH2:34][S:35][C@H:30]12.C[Si](CC(N)=O)(C)C>O1CCCC1.C(Cl)Cl.C(OCC)(=O)C.CN(C)C=O>[CH2:6]([O:13][C:14]([CH2:16][O:17][N:18]=[C:19]([C:23](=[O:26])[CH2:24][Br:25])[C:20]([NH:28][CH:29]1[C:54](=[O:55])[N:31]2[C:32]([C:38]([O:40][CH:41]([C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)[C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[O:39])=[C:33]([CH:36]=[CH2:37])[CH2:34][S:35][C@H:30]12)=[O:22])=[O:15])[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

9

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 12818005Benzhydryl 7-amino-3vinyl-3cephem-4-carboxylate hydrochlorideHCID 540321592-Benzyloxycarbonylmethoxyimino-4-bromo-3-oxobutyric acid

Product 1

HCID 131713331Benzhydryl 7-(2-benzyloxycarbonylmethoxyimino-4-bromo-3-oxobutyramido)-3-vinyl-3-cephem-4-carboxylateYield 74.5%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Vilsmeir reagent prepared from N,N-dimethylformamide (0.67 ml) and phosphorus oxychloride (0.79 ml) was suspended in dry tetrahydrofuran (25 ml). Thereto was added 2-benzyloxycarbonylmethoxyimino-4-bromo-3-oxobutyric acid (2.8 g) at 0° C. with stirring, and the stirring was continued at 0° to 5° C. for an hour to prepare the activated acid solution. This activated acid solution was added at a time to a solution of benzhydryl 7-amino-3-vinyl-3-cephem-4-carboxylate hydrochloride (2.2 g) and trimethylsilylacetamide (7.0 g) in methylene chloride (30 ml) at -35° C., and the mixture was stirred at -10° to -5° C. for 30 minutes. The reaction mixture was poured into ethyl acetate (200 ml), and the separated organic solution was washed with a saturated aqueous sodium bicarbonate and a saturated aqueous sodium chloride, followed by drying over magnesium sulfate. Removal of the solvent gave benzhydryl 7-(2-benzyloxycarbonylmethoxyimino-4-bromo-3-oxobutyramido)-3-vinyl-3-cephem-4-carboxylate (2.8 g).

Workup

  1. waitthe stirring was continued at 0° to 5° C. for an hour
  2. customto prepare the activated acid solution
  3. stirringthe mixture was stirred at -10° to -5° C. for 30 minutes
  4. washthe separated organic solution was washed with a saturated aqueous sodium bicarbonate
  5. dry with materialby drying over magnesium sulfate
  6. customRemoval of the solvent

Sources & evidence

ORD record
ord-f836bf6ef11544a798b5b68d56927d4d
Source dataset
uspto-grants-1993_10
Patent number
US05252731

Reaction notes

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